In this chapter, we discuss four adaptive randomised platform trials as case studies. We review two of the longest ongoing platform trials and another two important examples of ongoing platform trials conducted for COVID-19.

In this chapter, we discuss the key concepts, terminologies, and principles of master protocols. The term ‘master protocol’ is often misunderstood and misused. This term refers to a single overarching protocol document that is developed with the intention of evaluating multiple interventional hypotheses. ‘Master protocol’ itself does not refer to a specific type of clinical trial. There are three types of clinical trials that are conducted using the master protocol framework: platform trials, basket trials, and umbrella trials. While master protocols can naturally extend to adaptive trial designs, the use of adaptive trial designs is not a defining feature of master protocols nor of platform, basket, and umbrella trials. Master protocols implement common screening, trial systems, and standardised operating procedures across multiple trial institutions under one centralised governance model. In addition to statistical efficiencies, operational efficiencies can be gained by adopting the master protocol framework.

In this chapter, we review the concept of platform trials in close detail. Platform trials refer to clinical trials that allow new interventions to be added to the platform over time even, if they are not pre-specified in the design stage. Platform trials can be applied to all phases of clinical trial research. While they are most often conducted as randomised clinical trials with adaptive trial designs (adaptive platform randomised trials), they can be conducted with non-randomised or fixed sample trial designs as well. As a general goal, platform trials aim to establish a shared trial infrastructure where multiple interventions can be evaluated. Independent clinical trial evaluation would result in multiple separate teams creating shorter term infrastructure and trials that would otherwise compete against each other. Platform trials represent an exciting turning point for clinical research. The key design considerations of platform trials are outlined in this chapter.

The ongoing European Prevention of Alzheimer’s Dementia Programme (EPAD) was established in 2015 to create a platform for Phase 2 testing of interventions for the secondary prevention of Alzheimer’s disease (AD) dementia. This initiative was the largest of its kind globally. The original funding from the Innovative Medicines Initiative ensured that through their public-private partnership model, the programme benefited from expertise, know-how, and resources from academia, the pharmaceutical arena and third sector. Setting the vision, managing the innovative programme and operationalising scores of crucial and interdependent elements was a substantial governance and project management undertaking. The programme is ongoing with data and samples accessible through state-of-the-art systems in partnership with the Alzheimer’s Disease Data Interoperability programme. Follow-up of research participants is being organised and their involvement in a range of clinical trials is being facilitated via collaboration with the Global Alzheimer’s Platform. The challenges and lessons learned from EPAD are important as the field continued to advance and new therapies are developed.

Alzheimer’s disease (AD) drug development is a complex process that proceeds from identification of a biological target; to testing of candidate therapies in in vitro assays; assessment of efficacy in animal models and assessment of safety in several animal species; clinical testing in humans in Phase1, Phase 2, and Phase 3 clinical trials; regulatory review by agencies in all countries in which the drug might be marketed; and eventual commercialization. This process requires more than a decade to accomplish. The process involves substantial infrastructure resources; multiple stakeholders; and funding from a variety sources along the developmental pathway. This is the complex ecosystem that supports AD drug development.